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- EMDB-22872: Cryo-EM structure of the human arginine vasopressin AVP-vasopress... -

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Basic information

Entry
Database: EMDB / ID: EMD-22872
TitleCryo-EM structure of the human arginine vasopressin AVP-vasopressin receptor V2R-Gs signaling complex
Map dataV2R unsharpen map
Sample
  • Complex: Vasopressin V2 receptor complex with Gs and AVP
    • Complex: Vasopressin V2 receptor, Arg-vasopressinVasopressin receptor 2
      • Protein or peptide: Vasopressin V2 receptorVasopressin receptor 2
      • Protein or peptide: Arg-vasopressinVasopressin
    • Complex: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Single Fab chain (scFv16)
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
      • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-3, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short fusion
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
      • Protein or peptide: Single Fab chain (scFv16)
    • Complex: Nanobody 35Single-domain antibody
      • Protein or peptide: Nanobody 35Single-domain antibody
Function / homology
Function and homology information


V1B vasopressin receptor binding / Defective AVP does not bind AVPR1A,B and causes neurohypophyseal diabetes insipidus (NDI) / maternal aggressive behavior / Transport of organic anions / neurohypophyseal hormone activity / V1A vasopressin receptor binding / penile erection / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / regulation of renal sodium excretion ...V1B vasopressin receptor binding / Defective AVP does not bind AVPR1A,B and causes neurohypophyseal diabetes insipidus (NDI) / maternal aggressive behavior / Transport of organic anions / neurohypophyseal hormone activity / V1A vasopressin receptor binding / penile erection / renal water retention / Defective AVP does not bind AVPR2 and causes neurohypophyseal diabetes insipidus (NDI) / regulation of renal sodium excretion / negative regulation of transmission of nerve impulse / Vasopressin-like receptors / regulation of systemic arterial blood pressure by vasopressin / vasopressin receptor activity / negative regulation of female receptivity / protein kinase C signaling / hyperosmotic salinity response / water transport / hemostasis / positive regulation of systemic arterial blood pressure / telencephalon development / grooming behavior / positive regulation of prostaglandin biosynthetic process / negative regulation of adenylate cyclase activity / membrane organization / maternal behavior / neuropeptide hormone activity / vasoconstriction / renal water homeostasis / positive regulation of glutamate secretion / GTP metabolic process / positive regulation of intracellular signal transduction / dopamine receptor signaling pathway / response to testosterone / negative regulation of release of cytochrome c from mitochondria / social behavior / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / positive regulation of macroautophagy / endocytic vesicle / Adenylate cyclase inhibitory pathway / positive regulation of vasoconstriction / cellular response to hormone stimulus / negative regulation of inflammatory response to antigenic stimulus / activation of adenylate cyclase activity / ERK1 and ERK2 cascade / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / positive regulation of cellular pH reduction / BMAL1:CLOCK,NPAS2 activates circadian gene expression / locomotory behavior / secretory granule / generation of precursor metabolites and energy / response to cytokine / G protein-coupled receptor binding / peptide binding / response to nicotine / clathrin-coated endocytic vesicle membrane / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / Cargo recognition for clathrin-mediated endocytosis / retina development in camera-type eye
Similarity search - Function
Neurohypophysial hormone / Neurohypophysial hormone, conserved site / Neurohypophysial hormone domain superfamily / Neurohypophysial hormones, C-terminal Domain / Neurohypophysial hormones, N-terminal Domain / Neurohypophysial hormones signature. / Neurohypophysial hormones / Vasopressin V2 receptor / Vasopressin receptor / G-protein alpha subunit, group I ...Neurohypophysial hormone / Neurohypophysial hormone, conserved site / Neurohypophysial hormone domain superfamily / Neurohypophysial hormones, C-terminal Domain / Neurohypophysial hormones, N-terminal Domain / Neurohypophysial hormones signature. / Neurohypophysial hormones / Vasopressin V2 receptor / Vasopressin receptor / G-protein alpha subunit, group I / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Vasopressin-neurophysin 2-copeptin / Guanine nucleotide-binding protein G(i) subunit alpha-3 / Vasopressin V2 receptor / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Similarity search - Component
Biological speciesHomo sapiens (human) / Lama glama (llama)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.8 Å
AuthorsWang L / Xu J / Gao S / Sun D / Liu H / Liu Z / Du Y / Zhang C
Funding support United States, 1 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM128641 United States
CitationJournal: Cell Res / Year: 2021
Title: Cryo-EM structure of the AVP-vasopressin receptor 2-G signaling complex.
Authors: Lei Wang / Jun Xu / Sheng Cao / Dapeng Sun / Heng Liu / Qiuyuan Lu / Zheng Liu / Yang Du / Cheng Zhang /
History
DepositionOct 19, 2020-
Header (metadata) releaseMay 26, 2021-
Map releaseMay 26, 2021-
UpdateMar 29, 2023-
Current statusMar 29, 2023Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.3
  • Imaged by UCSF Chimera
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  • Surface view colored by height
  • Surface level: 0.3
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-7kh0
  • Surface level: 0.3
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_22872.png

Downloads & links

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Map

FileDownload / File: emd_22872.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationV2R unsharpen map
Voxel sizeX=Y=Z: 0.85 Å
Density
Contour LevelBy AUTHOR: 0.3 / Movie #1: 0.3
Minimum - Maximum-0.53609854 - 1.3442911
Average (Standard dev.)0.0026019297 (±0.050560948)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 217.6 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.850.850.85
M x/y/z256256256
origin x/y/z0.0000.0000.000
length x/y/z217.600217.600217.600
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS256256256
D min/max/mean-0.5361.3440.003

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Supplemental data

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Sample components

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Entire : Vasopressin V2 receptor complex with Gs and AVP

EntireName: Vasopressin V2 receptor complex with Gs and AVP
Components
  • Complex: Vasopressin V2 receptor complex with Gs and AVP
    • Complex: Vasopressin V2 receptor, Arg-vasopressinVasopressin receptor 2
      • Protein or peptide: Vasopressin V2 receptorVasopressin receptor 2
      • Protein or peptide: Arg-vasopressinVasopressin
    • Complex: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Single Fab chain (scFv16)
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
      • Protein or peptide: Guanine nucleotide-binding protein G(i) subunit alpha-3, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short fusion
      • Protein or peptide: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
      • Protein or peptide: Single Fab chain (scFv16)
    • Complex: Nanobody 35Single-domain antibody
      • Protein or peptide: Nanobody 35Single-domain antibody

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Supramolecule #1: Vasopressin V2 receptor complex with Gs and AVP

SupramoleculeName: Vasopressin V2 receptor complex with Gs and AVP / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

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Supramolecule #2: Vasopressin V2 receptor, Arg-vasopressin

SupramoleculeName: Vasopressin V2 receptor, Arg-vasopressin / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1, #4
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,...

SupramoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I) ...Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Single Fab chain (scFv16)
type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3, #5-#6
Source (natural)Organism: Homo sapiens (human)

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Supramolecule #4: Nanobody 35

SupramoleculeName: Nanobody 35 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #7
Source (natural)Organism: Lama glama (llama)

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Macromolecule #1: Vasopressin V2 receptor

MacromoleculeName: Vasopressin V2 receptor / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 42.34609 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: DYKDDDDVDM LMASTTSAVP GHPSLPSLPS NSSQERPLDT RDPLLARAEL ALLSIVFVAV ALSNGLVLAA LARRGRRGHW APIHVFIGH LCLADLAVAL FQVLPQLAWK ATDRFRGPDA LCRAVKYLQM VGMYASSYMI LAMTLDRHRA ICRPMLAYRH G SGAHWNRP ...String:
DYKDDDDVDM LMASTTSAVP GHPSLPSLPS NSSQERPLDT RDPLLARAEL ALLSIVFVAV ALSNGLVLAA LARRGRRGHW APIHVFIGH LCLADLAVAL FQVLPQLAWK ATDRFRGPDA LCRAVKYLQM VGMYASSYMI LAMTLDRHRA ICRPMLAYRH G SGAHWNRP VLVAWAFSLL LSLPQLFIFA QRNVEGGSGV TDCWACFAEP WGRRTYVTWI ALMVFVAPTL GIAACQVLIF RE IHASLVP GPSERPGGRR RGRRTGSPGE GAHVSAAVAK TVRMTLVIVV VYVLCWAPFF LVQLWAAWDP EAPLEGAPFV LLM LLASLN SCTNPWIYAS FSSSVSSELR SLLCCARGRT PPSLGPQDES CTTASSSLAK DTSSAAALEV LFQ

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Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 38.613176 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: HHHHHHGSLL QSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...String:
HHHHHHGSLL QSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN

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Macromolecule #3: Guanine nucleotide-binding protein G(i) subunit alpha-3, Isoform ...

MacromoleculeName: Guanine nucleotide-binding protein G(i) subunit alpha-3, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short fusion
type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.298055 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: GCTLSAEDKA AVERSKMIEK QLQKDKQVYR ATHRLLLLGA GESGKSTIVK QMRILHVNGF NGDSEKATKV QDIKNNLKEA IETIVAAMS NLVPPVELAN PENQFRVDYI LSVMNVPDFD FPPEFYEHAK ALWEDEGVRA CYERSNEYQL IDCAQYFLDK I DVIKQDDY ...String:
GCTLSAEDKA AVERSKMIEK QLQKDKQVYR ATHRLLLLGA GESGKSTIVK QMRILHVNGF NGDSEKATKV QDIKNNLKEA IETIVAAMS NLVPPVELAN PENQFRVDYI LSVMNVPDFD FPPEFYEHAK ALWEDEGVRA CYERSNEYQL IDCAQYFLDK I DVIKQDDY VPSDQDLLRC RVLTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVAS SSYNMVIRED NQ TNRLQEA LNLFKSIWNN RWLRTISVIL FLNKQDLLAE KVLAGKSKIE DYFPEFARYT TPEDATPEPG EDPRVTRAKY FIR DEFLRI STASGDGRHY CYPHFTCAVD TENIRRVFND CRDIIQRMHL RQYELL

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Macromolecule #4: Arg-vasopressin

MacromoleculeName: Arg-vasopressin / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 1.086248 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
CYFQNCPRG(NH2)

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Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

MacromoleculeName: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 7.432554 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString:
ASNNTASIAQ ARKLVEQLKM EANIDRIKVS KAAADLMAYC EAHAKEDPLL TPVPASENPF REKKFFC

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Macromolecule #6: Single Fab chain (scFv16)

MacromoleculeName: Single Fab chain (scFv16) / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 26.450531 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGLSVSISC R SSKSLLHS ...String:
DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGLSVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL K

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Macromolecule #7: Nanobody 35

MacromoleculeName: Nanobody 35 / type: protein_or_peptide / ID: 7 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Lama glama (llama)
Molecular weightTheoretical: 14.71432 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSH HHHHH

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Electron beamAcceleration voltage: 300 kV / Electron source: OTHER
Electron opticsIllumination mode: OTHER / Imaging mode: OTHER
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 55.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Initial angle assignmentType: OTHER
Final angle assignmentType: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 398038

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